tbuckley/cabot-search huggingface dataset:
The effects of night-time warming on mortality burden under future climate change scenarios: a modelling study
Authors: Cheng He, Ho Kim, Masahiro Hashizume, Whanhee Lee, Yasushi Honda, Satbyul Estella Kim, Patrick L Kinney, Alexandra Schneider, Yuqiang Zhang, Yixiang Zhu, Lu Zhou, Renjie Chen, Haidong Kan
Journal: The Lancet Planetary Health (2022)

<h2>Summary</h2><h3>Background</h3> The health impacts of climate warming are usually quantified based on daily average temperatures. However, extra health risks might result from hot nights. We project the future mortality burden due to hot nights. <h3>Methods</h3> We selected the hot night excess (HNE) to represent the intensity of night-time heat, which was calculated as the excess sum of high temperature during night time. We collected historical mortality data in 28 cities from three east Asian countries, from 1981 to 2010. The associations between HNE and mortality in each city were firstly examined using a generalised additive model in combination with a distributed lag non-linear model over lag 0–10 days. We then pooled the cumulative associations using a univariate meta-regression model at the national or regional levels. Historical and future hourly temperature series were projected under two scenarios of greenhouse-gas emissions from 1980–2099, with ten general circulation models. We then projected the attributable fraction of mortality due to HNE under each scenario. <h3>Findings</h3> Our dataset comprised 28 cities across three countries (Japan, South Korea, and China), including 9 185 598 deaths. The time-series analyses showed the HNE was significantly associated with increased mortality risks, the relative mortality risk on days with hot nights could be 50% higher than on days with non-hot nights. Compared with the rise in daily mean temperature (lower than 20%), the frequency of hot nights would increase more than 30% and the intensity of hot night would increase by 50% by 2100s. The attributable fraction of mortality due to hot nights was projected to be 3·68% (95% CI 1·20 to 6·17) under a strict emission control scenario (SSP126). Under a medium emission control scenario (SSP245), the attributable fraction of mortality was projected to increase up to 5·79% (2·07 to 9·52), which is 0·95% (−0·39 to 2·29) more than the attributable fraction of mortality due to daily mean temperature. <h3>Interpretation</h3> Our study provides evidence for significant mortality risks and burden in association with night-time warming across Japan, South Korea, and China. Our findings suggest a growing role of night-time warming in heat-related health effects in a changing climate. <h3>Funding</h3> The National Natural Science Foundation of China, Shanghai International Science and Technology Partnership Project.
Vulnerability and One Health assessment approaches for infectious threats from a social science perspective: a systematic scoping review
Authors: Maren Jeleff, Lisa Lehner, Tamara Giles-Vernick, Michel L A Dückers, A David Napier, Elena Jirovsky-Platter, Ruth Kutalek
Journal: The Lancet Planetary Health (2022)

Vulnerability assessments identify vulnerable groups and can promote effective community engagement in responding to and mitigating destabilising events. This scoping review maps assessments for local-level vulnerabilities in the context of infectious threats. We searched various databases for articles written between 1978 and 2019. Eligible documents assessed local-level vulnerability, focusing on infectious threats and antimicrobial resistance. Since few studies provided this dual focus, we included tools from climate change and disaster risk reduction literature that engaged the community in the assessment. We considered studies using a One Health approach as essential for identifying vulnerability risk factors for zoonotic disease affecting humans. Of the 5390 records, we selected 36 articles for review. This scoping review fills a gap regarding vulnerability assessments by combining insights from various approaches: local-level understandings of vulnerability involving community perspectives; studies of social and ecological factors relevant to exposure; and integrated quantitative and qualitative methods that make generalisations based on direct observation. The findings inform the development of new tools to identify vulnerabilities and their relation to social and natural environments.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2018)

Transcription factors (TF) contain structured DNA-binding domains and intrinsically disordered low complexity activation domains (LCD).Using single-molecule imaging in live cells, Chong and colleagues demonstrated that TF-LCD interactions were transient, sequence-specific, and aggregated to form clusters.These "hubs" of high TF concentrations were associated with genomic DNA and occurred throughout the nucleoplasm.TF-LCD puncta interacted with RNA polymerase II and drove transactivation.Using EWS-FL1 as a model, they showed that EWS LCD-LCD interactions at GGAA microsatellites were dynamic, selective for binding partners, and could be disrupted by hexanediols.Phase separation was not seen with endogenous levels of LCDs, but was observed at TF hubs upon forced expression of LCDs, suggesting a pathological feature.Expert Commentary: These findings represent an important advance to the understanding of gene regulation and offer opportunities to screen for inhibitors of LCD-LCD interactions.
CRISPR–Cas9-mediated gene editing of the BCL11A enhancer for pediatric β0/β0 transfusion-dependent β-thalassemia
Authors: Bin Fu, Jiaoyang Liao, Shuanghong Chen, Wei Li, Qiudao Wang, Jian Hu, Fei Yang, Shenlin Hsiao, Yanhong Jiang, Liren Wang, Fangping Chen, Yuanjin Zhang, Xin Wang, Dali Li, Mingyao Liu, Yuxuan Wu
Journal: Nature Medicine (2022)
Different aspects of severe asthma in real life: Role of <i>Staphylococcus aureus</i> enterotoxins and correlation to comorbidities and disease severity
Authors: Cristiano Caruso, Stefania Colantuono, Gabriele Ciasca, Umberto Basile, Riccardo Di Santo, Diego Bagnasco, Giovanni Passalacqua, Marco Caminati, Schiappoli Michele, Gianenrico Senna, Enrico Heffler, G. Walter Canonica, Nunzio Crimi, Rossella Intravaia, Eugenio De Corso, Davide Firinu, Antonio Gasbarrini, Stefano R. Del Giacco
Journal: Allergy (2022)

Abstract Background Asthma, with several phenotypes and endotypes, is considered particularly suited for precision medicine. The identification of different non‐invasive biomarkers may facilitate diagnosis and treatment. Recently, Staphylococcus aureus and its enterotoxins (SE) have been found to have a role in inducing persistent type 2 airway inflammation in severe asthma, but also in such comorbidities as chronic rhinosinusitis with nasal polyposis (CRSwNP). Methods The aim of this retrospective study was to evaluate the prevalence of SE‐IgE sensitization in a multicentric Italian cohort of severe asthmatic patients and correlate it with demographic and clinical characteristics. Results A total of 249 patients were included in the analysis, out of which 25.3% were staphylococcal enterotoxin B (SEB)‐IgE positive. We found a meaningful association between SEB‐IgE and female gender, a positive association was also measured between CRS and CRSwNP. No significant association was found between SEB‐IgE sensitization and atopy, the occurrence of exacerbations and corticosteroid dosages. In the SEB‐IgE‐positive patient, blood eosinophil count does not appear to be correlated with the severity of the disease. Patients with SEB‐IgE sensitization are, on average, younger and with an earlier disease onset, thus confirming the possibility to consider SEB‐IgE sensitization as an independent risk factor for developing asthma. Conclusions Our data confirm that the search for SE in the initial screening phase of these patients is helpful to better phenotype them, may predict the evolution of comorbidities and lead to a targeted therapeutic choice; in this point of view this represents a goal of precision medicine.
Targeting KRAS mutant cancers: from druggable therapy to drug resistance
Authors: Chunxiao Zhu, Xiaoqing Guan, Xinuo Zhang, Xin Luan, Zhengbo Song, Xiangdong Cheng, Weidong Zhang, Jiang-Jiang Qin
Journal: Molecular Cancer (2022)

Abstract Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) is the most frequently mutated oncogene, occurring in a variety of tumor types. Targeting KRAS mutations with drugs is challenging because KRAS is considered undruggable due to the lack of classic drug binding sites. Over the past 40 years, great efforts have been made to explore routes for indirect targeting of KRAS mutant cancers, including KRAS expression, processing, upstream regulators, or downstream effectors. With the advent of KRAS (G12C) inhibitors, KRAS mutations are now druggable. Despite such inhibitors showing remarkable clinical responses, resistance to monotherapy of KRAS inhibitors is eventually developed. Significant progress has been made in understanding the mechanisms of drug resistance to KRAS-mutant inhibitors. Here we review the most recent advances in therapeutic approaches and resistance mechanisms targeting KRAS mutations and discuss opportunities for combination therapy.
Survival Benefit of Living-Donor Liver Transplant
Authors: Whitney E. Jackson, John S. Malamon, Bruce Kaplan, Jessica L. Saben, Jesse D. Schold, James J. Pomposelli, Elizabeth A. Pomfret
Journal: JAMA Surgery (2022)

Despite the acceptance of living-donor liver transplant (LDLT) as a lifesaving procedure for end-stage liver disease, it remains underused in the United States. Quantification of lifetime survival benefit and the Model for End-stage Liver Disease incorporating sodium levels (MELD-Na) score range at which benefit outweighs risk in LDLT is necessary to demonstrate its safety and effectiveness.To assess the survival benefit, life-years saved, and the MELD-Na score at which that survival benefit was obtained for individuals who received an LDLT compared with that for individuals who remained on the wait list.This case-control study was a retrospective, secondary analysis of the Scientific Registry of Transplant Recipients database of 119 275 US liver transplant candidates and recipients from January 1, 2012, to September 2, 2021. Liver transplant candidates aged 18 years or older who were assigned to the wait list (N = 116 455) or received LDLT (N = 2820) were included. Patients listed for retransplant or multiorgan transplant and those with prior kidney or liver transplants were excluded.Living-donor liver transplant vs remaining on the wait list.The primary outcome of this study was life-years saved from receiving an LDLT. Secondary outcomes included 1-year relative mortality and risk, time to equal risk, time to equal survival, and the MELD-Na score at which that survival benefit was obtained for individuals who received an LDLT compared with that for individuals who remained on the wait list. MELD-Na score ranges from 6 to 40 and is well correlated with short-term survival. Higher MELD-Na scores (>20) are associated with an increased risk of death.The mean (SD) age of the 119 275 study participants was 55.1 (11.2) years, 63% were male, 0.9% were American Indian or Alaska Native, 4.3% were Asian, 8.2% were Black or African American, 15.8% were Hispanic or Latino, 0.2% were Native Hawaiian or Other Pacific Islander, and 70.2% were White. Mortality risk and survival models confirmed a significant survival benefit for patients receiving an LDLT who had a MELD-Na score of 11 or higher (adjusted hazard ratio, 0.64 [95% CI, 0.47-0.88]; P = .006). Living-donor liver transplant recipients gained an additional 13 to 17 life-years compared with patients who never received an LDLT.An LDLT is associated with a substantial survival benefit to patients with end-stage liver disease even at MELD-Na scores as low as 11. The findings of this study suggest that the life-years gained are comparable to or greater than those conferred by any other lifesaving procedure or by a deceased-donor liver transplant. This study's findings challenge current perceptions regarding when LDLT survival benefit occurs.
LPA <sub>2</sub> Contributes to Vascular Endothelium Homeostasis and Cardiac Remodeling After Myocardial Infarction
Authors: Jianqiu Pei, Lin Cai, Fang Wang, Chuansheng Xu, Shengqiang Pei, Hongwei Guo, Xiaogang Sun, Jerold Chun, Xiangfeng Cong, Weiquan Zhu, Zhe Zheng, Xi Chen
Journal: Circulation Research (2022)

Rationale: Myocardial infarction (MI) is one of the most dangerous adverse cardiovascular events. Our previous study found that lysophosphatidic acid (LPA) is increased in human peripheral blood after MI, and LPA has a protective effect on the survival and proliferation of various cell types. However, the role of LPA and its receptors in MI is less understood. Objectives: To study the unknown role of LPA and its receptors in heart during MI. Methods and Results: In this study, we found that mice also had elevated LPA level in peripheral blood, as well as increased cardiac expression of its receptor LPA 2 in the early stages after MI. With adult and neonate MI models in global Lpar2 knockout ( Lpar2 -KO) mice, we found Lpar2 deficiency increased vascular leak leading to disruption of its homeostasis, so as to impaired heart function and increased early mortality. Histological examination revealed larger scar size, increased fibrosis, and reduced vascular density in the heart of Lpar2 -KO mice. Furthermore, Lpar2 -KO also attenuated blood flow recovery after femoral artery ligation with decreased vascular density in gastrocnemius. Our study revealed that Lpar2 was mainly expressed and altered in cardiac endothelial cells during MI, and use of endothelial-specific Lpar2 knockout mice phenocopied the global knockout mice. Additionally, adenovirus- Lpar2 and pharmacologically activated LPA 2 significantly improved heart function, reduced scar size, increased vascular formation, and alleviated early mortality by maintaining vascular homeostasis owing to protecting vessels from leakage. Mechanistic studies demonstrated that LPA-LPA 2 signaling could promote endothelial cell proliferation through PI3K-Akt/PLC-Raf1-Erk pathway and enhanced endothelial cell tube formation via PKD1-CD36 signaling. Conclusions: Our results indicate that endothelial LPA-LPA 2 signaling promotes angiogenesis and maintains vascular homeostasis, which is vital for restoring blood flow and repairing tissue function in ischemic injuries. Targeting LPA-LPA 2 signal might have clinical therapeutic potential to protect the heart from ischemic injury.
Author Correction: Systematic identification of cell-fate regulatory programs using a single-cell atlas of mouse development
Authors: Lijiang Fei, Haide Chen, Lifeng Ma, Weigao E, Renying Wang, Xing Fang, Ziming Zhou, Huiyu Sun, Jingjing Wang, Mengmeng Jiang, Xinru Wang, Chengxuan Yu, Yuqing Mei, Danmei Jia, Tingyue Zhang, Xiaoping Han, Guoji Guo
Journal: Nature Genetics (2022)
Dermatological considerations and culturally sensitive recommendations for women who wear the hijab
Authors: Rafey Rehman, Mahfujul Haque, Marissa Ceresnie, Iltefat H. Hamzavi, Fatima Fahs, Tasneem F. Mohammad
Journal: British Journal of Dermatology (2022)

Currently, there is little guidance in the literature on how to advise patients who wear the hijab on hijab-related dermatoses. This manuscript describes hijab-related dermatoses and provides culturally sensitive recommendations that can be used in conjunction with standard treatments to provide more holistic care for these patients.
Where’s the colour? Advocating for morphological and antioppressive fluencies in dermatology
Authors: Gagandeep Singh, Onye Nnorom, Erin Dahlke
Journal: British Journal of Dermatology (2022)

The sociomedical drivers underpinning racial health disparities in dermatology are receiving increasing attention. Consistent and respectful language are required as we resist and dismantle racism in dermatology. Authors share two guiding principles learned from interweaving equity, diversity, and anti-oppression content into their institution’s dermatology curricula to maintain respect and dignity of racialized persons in dermatology research, education, and clinical practice communications.
Atrial amyloidosis: mechanisms and clinical manifestations
Authors: Giuseppe Vergaro, Alberto Aimo, Claudio Rapezzi, Vincenzo Castiglione, Iacopo Fabiani, Angela Pucci, Gabriele Buda, Claudio Passino, Josep Lupón, Antoni Bayes‐Genis, Michele Emdin, Eugene Braunwald
Journal: European Journal of Heart Failure (2022)

Cardiac amyloidosis (CA) is now recognized as an important cause of heart failure. Increased wall thickness and diastolic dysfunction of the left ventricle are the most easily detectable manifestations of CA, but amyloid accumulates in all cardiac structures. Involvement of the left and right atria may be due to the haemodynamic effects of ventricular diastolic dysfunction, the effects of amyloid infiltration into the atrial wall, and the cardiotoxic damage of atrial cardiomyocytes by amyloid precursors. Atrial amyloidosis is an early manifestation of CA, and is associated with an increased risk of atrial fibrillation and thromboembolic events. Furthermore, atrial amyloidosis can be found even in the absence of systemic disease and ventricular involvement. This condition is named isolated atrial amyloidosis and is due to a local overproduction of atrial natriuretic peptide. In this review we summarize the evidence on the mechanisms and clinical relevance of atrial amyloidosis.
Cutaneous Herpetiform Ulcerations as the Presenting Sign of an Acute Aortic Occlusion
Authors: Ryan Sacotte, Ashaki Patel, Karolyn A. Wanat, Kara Young, Gretchen Roth, Barbara Wilson
Journal: JAMA Dermatology (2022)

This case report describes a woman in her 40s with a 2-week history of abrupt painful ulcerations of the perineum.
Whole genome sequencing reveals the independent clonal origin of multifocal ileal neuroendocrine tumors
Authors: Netta Mäkinen, Meng Zhou, Zhouwei Zhang, Yosuke Kasai, Elizabeth Perez, Grace E. Kim, Chrissie Thirlwell, Eric Nakakura, Matthew Meyerson
Journal: Genome Medicine (2022)

Small intestinal neuroendocrine tumors (SI-NETs) are the most common neoplasms of the small bowel. The majority of tumors are located in the distal ileum with a high incidence of multiple synchronous primary tumors. Even though up to 50% of SI-NET patients are diagnosed with multifocal disease, the mechanisms underlying multiple synchronous lesions remain elusive.
Phylogenomic Evidence for the Origin of Obligate Anaerobic Anammox Bacteria Around the Great Oxidation Event
Authors: Tianhua Liao, Sishuo Wang, Eva E Stüeken, Haiwei Luo
Journal: Molecular Biology and Evolution (2022)

Abstract The anaerobic ammonium oxidation (anammox) bacteria can transform ammonium and nitrite to dinitrogen gas, and this obligate anaerobic process accounts for up to half of the global nitrogen loss in surface environments. Yet its origin and evolution, which may give important insights into the biogeochemistry of early Earth, remain enigmatic. Here, we performed a comprehensive phylogenomic and molecular clock analysis of anammox bacteria within the phylum Planctomycetes. After accommodating the uncertainties and factors influencing time estimates, which include implementing both a traditional cyanobacteria-based and a recently developed mitochondria-based molecular dating approach, we estimated a consistent origin of anammox bacteria at early Proterozoic and most likely around the so-called Great Oxidation Event (GOE; 2.32–2.5 Ga) which fundamentally changed global biogeochemical cycles. We further showed that during the origin of anammox bacteria, genes involved in oxidative stress adaptation, bioenergetics, and anammox granules formation were recruited, which might have contributed to their survival on an increasingly oxic Earth. Our findings suggest the rising levels of atmospheric oxygen, which made nitrite increasingly available, was a potential driving force for the emergence of anammox bacteria. This is one of the first studies that link the GOE to the evolution of obligate anaerobic bacteria.
Modulating Lysine Crotonylation in Cardiomyocytes Improves Myocardial Outcomes
Authors: Wenqian Cai, Dacai Xu, Chui Zeng, Fan Liao, Ruiqi Li, Yingjiong Lin, Yue Zhao, Wenyan Dong, Qingwen Wang, Haili Yang, Daqiang Wen, Jianbiao Gu, Weihui Shentu, Hongkui Yu, Xiaochun Zhang, Jianrui Wei, Jinzhu Duan
Journal: Circulation Research (2022)

Ischemic heart disease is a major global public health challenge, and its functional outcomes remain poor. Lysine crotonylation (Kcr) was recently identified as a post-translational histone modification that robustly indicates active promoters. However, the role of Kcr in myocardial injury is unknown. In this study, we aimed to clarify the pathophysiological significance of Kcr in cardiac injury and explore the underlying mechanism. We investigated the dynamic change of both the Kcr sites and protein level in left ventricular tissues at 2 time points following sham or cardiac ischemia-reperfusion injury, followed by liquid chromatography-coupled tandem mass tag mass spectrometry. After validation of the enriched protein Kcr by immunoprecipitation and Western blot, the function and mechanism of specific Kcr sites were further investigated in vitro and in vivo by gain- or loss-of-function mutations targeting Kcr sites of selected proteins. We found that cardiac ischemia-reperfusion injury triggers preferential Kcr of proteins required for cardiomyocyte contractility, including mitochondrial and cytoskeleton proteins, which occurs largely independently of protein-level changes in the same proteins. Those exhibiting Kcr changes were associated not only with disruption of cardiomyocyte mitochondrial, sarcomere architecture, and gap junction but also with cardiomyocyte autophagy and apoptosis. Modulating site-specific Kcr of selected mitochondrial protein IDH3a (isocitrate dehydrogenase 3 [NAD+] alpha) at K199 and cytoskeletal protein TPM1 (tropomyosin alpha-1 chain) at K28/29 or enhancing general Kcr via sodium crotonate provision not only protects cardiomyocyte from apoptosis by inhibiting BNIP3 (Bcl-2 adenovirus E18 19-kDa-interacting protein 3)-mediated mitophagy or cytoskeleton structure rearrangement but also preserves postinjury myocardial function by inhibiting fibrosis and apoptosis. Our results indicate that Kcr modulation is a key response of cardiomyocytes to ischemia-reperfusion injury and may represent a novel therapeutic target in the context of ischemic heart disease.
Composite Superelastic Aerogel Scaffolds Containing Flexible SiO<sub>2</sub> Nanofibers Promote Bone Regeneration (Adv. Healthcare Mater. 15/2022)
Authors: Mingyue Liu, Muhammad Shafiq, Binbin Sun, Jinglei Wu, Wei Wang, Mohamed EL‐Newehy, Hany EL‐Hamshary, Yosry Morsi, Onaza Ali, Atta ur Rehman Khan, Xiumei Mo
Journal: Advanced Healthcare Materials (2022)

Hybrid Aerogel Scaffolds In article number 2200499 by Xiumei Mo and co-workers, inorganic-organic hybrid aerogel scaffolds are prepared by hybrid thermal crosslinking of organic poly lactic acid (PLA)/gel electrospun short nanofibers and flexible SiO2 electrospun short nanofibers. The electrospun nanofibrous aerogel scaffolds have excellent elasticity and porous structure, which enables them to have good shape memory for intimately filled articular bone defects. The silicon ions released from the PLA/gel/SiO2 aerogel scaffold with porous nanofibrous structure can promote the formation of blood vessels and the expression of bone-related genes, thereby promoting the regeneration of rat calvaria.